Despite attractive, ionizing radiations cannot be directly applied in the treatment of bacterial infections since bacteria are extremely insensitive to radiations. The lethal radiation dose for bacteria is at least 1,000 times higher than the whole-body lethal dose for human. In this R21 project, we propose a novel intracellular radiation approach to activate a secondary and local radiation inside of bacteria to damage chromosomal DNAs selectively and specifically. The underlying hypothesis of this project is that: this intracellular radiation can overcome the radiation resistance in bacteria, and the intracellular radiation by itself or in combination with antibiotics may become an effective means to kill antibiotic resistance bacteria. The primary goal of this grant is to achieve the "proof-of-concept" via well designed in vitro studies. The success of this project may provide a new approach for improved the treatment of bacterial infections and various infection related diseases. PUBLIC HEALTH RELEVANCE: Intracellular Radiation as a Novel Approach for Infection Treatment Narrative Bacteria is resistant to ionizing radiations. The lethal radiation dose (1,000 Gy to 6,000 Gy) for bacteria is far beyond the whole-body lethal dose for human (5 Gy) and thus limits the potential applications of ionizing radiation in the treatment of antibiotics resistance. In this project, we propose a novel intracellular radiation approach to overcome the radiation resistance in bacteria and explore the clinical applications of radiations in the treatment of bacterial infections and various infection related diseases.